The Fanconi anemia polypeptide FACC is localized to the cytoplasm.

Yamashita, Takayuki; Barber, Dwayne L.; Zhu, Yanfei; Wu, Nan; D’Andrea, Alan D.

doi:10.1073/pnas.91.14.6712

Cited by 131 publications

(52 citation statements)

References 22 publications

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“…Yamashita et al (5) have also observed a similar association of FAC with cellular proteins in immunocomplexes. Although these studies suggest that FAC is capable of forming a multimeric complex in vitro, the biological significance of these associations is unclear.…”

Section: Introductionmentioning

confidence: 68%

Induction of Fanconi anemia cellular phenotype in human 293 cells by overexpression of a mutant FAC allele.

Youssoufian

Li²,

Martin³

et al. 1996

J. Clin. Invest.

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Section: Introductionmentioning

confidence: 68%

Induction of Fanconi anemia cellular phenotype in human 293 cells by overexpression of a mutant FAC allele.

Youssoufian

Li²,

Martin³

et al. 1996

J. Clin. Invest.

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“…13,14 The human FANCG has a putative leucine zipper motif, but it is not conserved in the mammalian homologs. 15 FANCC has a predominantly cytoplasmic localization, 16,17 with a smaller fraction present in the nucleus. 18 The FANCA, FANCF, and FANCG proteins are found predominantly in the nucleus, with some cytoplasmic localization.…”

Section: Introductionmentioning

confidence: 99%

Fanconi anemia protein complex: mapping protein interactions in the yeast 2- and 3-hybrid systems

Gordon

Buchwald

2003

Blood

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IntroductionFanconi anemia (FA) is a rare autosomal recessive syndrome characterized by pancytopenia, predisposition to cancer, and a wide range of congenital malformations. 1 Cells from patients with FA exhibit elevated spontaneous chromosome breakage and are hypersensitive to DNA cross-linking agents, including mitomycin C and diepoxybutane. 2 FA is a genetically heterogeneous disorder comprising at least 8 complementation groups (FA-A, -B, -C, -D1, -D2, -E, -F, -G), 3,4 the genes for 6 of which (FANCA,5,6 FANCC, 7 FANCD2, 4 FANCE, 8 FANCF,9 and FANCG 10 ) have been cloned. Most recently biallelic inactivation of BRCA2 was identified in FA cell lines from complementation groups With the exception of FANCD2, which has conserved sequences in Arabidopsis thaliana, Drosophila melanogaster, and Caenorhabditis elegans, FANC protein orthologs have not been identified in nonvertebrates. 12 In addition, despite the similar clinical phenotype generated by their individual absence, the FANC proteins do not bear any sequence similarity to each other. This phenomenon has given rise to the question of how, when, and where these orphan proteins might interact to maintain genomic integrity.Database searches have revealed few identifiable proteininteraction motifs among the FANC proteins. Neither FANCC nor FANCF contain any such motifs. FANCE has a putative nuclear localization signal (NLS) in the central region of its sequence. 8 FANCA has overlapping bipartite nuclear localization signals at the amino-terminus of the protein and a more carboxyl-terminal leucine zipper motif 5,6 that are conserved in the mouse homolog. 13,14 The human FANCG has a putative leucine zipper motif, but it is not conserved in the mammalian homologs. 15 FANCC has a predominantly cytoplasmic localization, 16,17 with a smaller fraction present in the nucleus. 18 The FANCA, FANCF, and FANCG proteins are found predominantly in the nucleus, with some cytoplasmic localization. [19][20][21][22][23] FANCE has recently been shown to localize to the nucleus, concentrated in foci. 24 FANCD2 is localized entirely to the nucleus, predominantly in a diffuse pattern, but also with a subset of cells containing foci. 25 In addition to these variations in cellular compartmentalization, some FANC proteins appear to be involved in the localization of others, such as the ability of FANCE to promote the nuclear accumulation of FANCC. 24 The FANCA, FANCC, and FANCG proteins immunoprecipitate as a complex, 21,26 which has been shown to localize to chromatin and the nuclear matrix. 27 The FANCF and FANCE proteins have also been identified in this nuclear complex, 23,24 the formation of which is disrupted in cell lines from FA complementation groups FA-A, -B, -C, -E, -F, and -G. 23,28,29 The FANCD2 protein, believed to function downstream of the FA protein complex, has been immunoprecipitated only with FANCE. 24 In the absence of complex formation FANCD2 is not monoubiquinated or targeted to nuclear foci in response to DNA-damaging agents. 25 Several direct interactions ha...

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“…The FANCC gene, cloned by functional complementation of FA-C cells, encodes a protein of 558 amino acids with a molecular mass of 63 kd. 8 The cellular localization of FANCC protein is mostly cytoplasmic, 14,15 but a fraction of this protein does translocate into nuclei. [16][17][18][19] The FANCA gene encodes a protein of 1455 amino acids with a molecular mass of approximately 163 kd.…”

Section: Introductionmentioning

confidence: 99%

A cytoplasmic serine protein kinase binds and may regulate the Fanconi anemia protein FANCA

Yagasaki

Adachi²,

Oda³

et al. 2001

Blood

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IntroductionFanconi anemia (FA) is an autosomal recessive disease characterized by congenital anomalies, progressive bone marrow failure, and susceptibility to leukemia (reviewed by Buchwald and Moustacchi 1 and Garcia-Higuera and colleagues 2 ). Cells derived from patients with FA show chromosomal instability, hypersensitivity to DNA cross-linking agents such as mitomycin C (MMC), abnormal cell cycle progression, and reduced cell survival. 1,2 FA has at least 8 different complementation groups (FA-A to FA-G) as defined by cell fusion analysis. [3][4][5][6][7] To date, 6 of the FA genes (FANCA, FANCC, FANCD2, FANCE, FANCF, and FANCG) have been cloned. [7][8][9][10][11][12][13] The FA proteins have no functional domains, such as protein kinase (PK) and DNA helicase motifs, and no homology to each other or other known proteins. The FANCC gene, cloned by functional complementation of FA-C cells, encodes a protein of 558 amino acids with a molecular mass of 63 kd. 8 The cellular localization of FANCC protein is mostly cytoplasmic, 14,15 but a fraction of this protein does translocate into nuclei. [16][17][18][19] The FANCA gene encodes a protein of 1455 amino acids with a molecular mass of approximately 163 kd. 9,10 The protein contains a bipartite nuclear localization signal (NLS) at its N-terminus and a partial leucine zipper between amino acids 1069 and 1090. This protein is detected both in the nuclei and in the cytoplasm. [16][17][18][19] The FANCG gene cloned by its potential to complement FA-G cells is identical to the previously identified human XRCC9 gene, cloned by its potential to partially complement sensitivity to DNA-damaging agents of a mutant Chinese hamster ovary (CHO) cell line. 11,20 This gene encodes a 68-kd protein with an internal leucine zipper. The FANCF and FANCE genes, cloned by functional complementation, encode a nuclear 42-kd protein and a 60-kd protein with 2 NLS motifs, respectively. 12,13 The FANCD2 gene, cloned positionally, encodes a 163-kd nuclear protein. 7 This protein is monoubiquitinated in response to DNA damage and interacts with the breast cancer susceptibility protein, BRCA1, in nuclear foci. 21 A number of studies from our group 16,18,[22][23][24][25] and others [26][27][28][29] indicate that the protein complex assembly of FANCA, FANCC, and FANCG in the cytoplasm and nuclear accumulation of the protein complex play a crucial role in the FA pathway. FANCF and FANCE are likely to assemble in the protein complex in nuclei. 11,12,29 Defects of either of these FA proteins abrogate monoubiquitination and targeting to nuclear foci of FANCD2. 21 These findings support a proposal of the FA pathway that the multiple FA proteins sequentially assemble and finally activate FANCD2, a downstream nuclear component of the pathway. 18,21,29 Thus, this pathway appears to regulate nuclear functions such as DNA repair, replication, and transcription. On the other hand, significant amounts of FANCA, FANCC, and FANCG proteins localize in the cytoplasm and these proteins interact with various ...

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The Fanconi anemia polypeptide FACC is localized to the cytoplasm.

Abstract: ABSTRACT

Cited by 131 publications

References 22 publications

Induction of Fanconi anemia cellular phenotype in human 293 cells by overexpression of a mutant FAC allele.

Induction of Fanconi anemia cellular phenotype in human 293 cells by overexpression of a mutant FAC allele.

Fanconi anemia protein complex: mapping protein interactions in the yeast 2- and 3-hybrid systems

A cytoplasmic serine protein kinase binds and may regulate the Fanconi anemia protein FANCA

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